Human Esophageal Cancer Research Articles

Aluminium phthalocyanine-mediated photodynamic therapy induces ATM-related DNA damage response and apoptosis in human oesophageal cancer cells.

Photodynamic therapy (PDT) is a light-based technique used in the treatment of malignant and non-malignant tissue. Aluminium-phthalocyanine chloride tetra sulfonate (AlPcS4Cl)-mediated PDT has been well investigated on several cancer types, including oesophageal cancer. However, the effects of (AlPcS4Cl)-mediated PDT on DNA damage response and the mechanism of cell death in oesophageal cancer needs further investigation. Here, we examined the in vitro effects of AlPcS4Cl-mediated PDT on cell cycle, DNA damage response, oxidative stress, and intrinsic apoptotic cell death pathway in HKESC-1 oesophageal cancer cells. The HKESC-1 cells were exposed to PDT using a semiconductor laser diode (673.2 nm, 5 J/cm2 fluency). Cell viability and cytotoxicity were determined by the ATP cell viability assay and the lactate dehydrogenase (LDH) release assay, respectively. Cell cycle and DNA damage response (DDR) analyses were conducted using the Muse™ cell cycle kit and the Muse® multi-color DNA damage kit, respectively. The mode of cell death was identified using the Annexin V-FITC/PI detection assay and Muse® Autophagy LC3 antibody-based kit. The intrinsic apoptotic pathway was investigated by measuring the cellular reactive oxygen species (ROS) levels, mitochondrial membrane potential (ΔΨm) function, cytochrome c levels and the activity of caspase 3/7 enzymes. The results show that AlPcS4Cl-based PDT reduced cell viability, induced cytotoxicity, cell cycle arrest at the G0/G1 phase, and DNA double-strand break (DSB) through the upregulation of the ataxia telangiectasia mutated (ATM), a DNA damage sensor. In addition, the findings showed that AlPcS4Cl-based PDT induced cell death via apoptosis, which is observed through increased ROS production, reduced ΔΨm, increased cytochrome c release, and activation of caspase 3/7 enzyme. Finally, no autophagy was observed in the AlPcS4Cl-mediated PDT-treated cells. Our findings showed that apoptotic cell death is the main cell death mechanism triggered by AlPcS4Cl-mediated PDT in oesophageal cancer cells.

Screening The Anticancer Activity for New Schiff Bases of Natural Steroids

The significance of cholesterol and ergosterol (provitamin d2) in biological systems has prompted interest in these compounds as pharmaceuticals. It has been reported on the effective straightforward synthesis of Schiff base modifications of cholesterol aldehyde and ergosterol aldehyde and their assessment as possible agents against cancer (esophagus natural cell lines and human cancer cells). Through a process called Steglish esterification, the initial cholesterol and ergosterol are converted into their respective aldehyde derivatives, by reacting with amines such as 2-amino 6-fluoro benzothiazole, carbohydrazide, and thiosemicarbazide, these aldehyde derivatives are transformed into the appropriate Schiff base derivatives, and then their anticancer activity is checked using the MTT (Microculture Tetrazolium Assay) assay method. For the purpose of analyzing their cytotoxic effects, these compounds were tested on cancerous (SK-GT-4, human esophageal adenocarcinoma) and normal (normal cell line, Rat Embryonic fibroblast (REF)) cell lines. The MTT assay results revealed that the compounds (a1, a2, c1, c2, compound 1) were more harmful to human esophageal cancer cell line than to healthy cell line other than compounds (t1, t2, compound 2, ergosterol and cholesterol alone). Overall, our research indicated that provitamin D2 (ergosterol), a1, a2, c2, t2, compound 1, had a growth-inhibiting effect on both cell lines compared to c1, t1, compound 2, and cholesterol alone.

MiR-199a-5p Decreases Esophageal Cancer Cell Proliferation Partially through Repression of Jun-B.

MicroRNA (miR)-199a-5p has been shown to function as a tumor suppressor in some malignancies but its role in esophageal cancer is poorly understood. To further explore its role in esophageal cancer, we sought to investigate the interaction between miR-199a-5p and Jun-B, an important component of the AP1 transcription factor, which contains a potential binding site for miR-199a-5p in its mRNA. We found that levels of miR-199a-5p are reduced in both human esophageal cancer specimens and in multiple esophageal cancer cell lines compared to esophageal epithelial cells. Jun-B expression is correspondingly elevated in these tumor specimens and in several cell lines compared to esophageal epithelial cells. Jun-B mRNA expression and stability, as well as protein expression, are markedly decreased following miR-199a-5p overexpression. A direct interaction between miR-199a-5p and Jun-B mRNA was confirmed by a biotinylated RNA-pull down assay and luciferase reporter constructs. Either forced expression of miR-199a-5p or Jun-B silencing led to a significant decrease in cellular proliferation as well as in AP-1 promoter activity. Our results provide evidence that miR-199a-5p functions as a tumor suppressor in esophageal cancer cells by regulating cellular proliferation, partially through repression of Jun B.

Endogenous hydrogen sulfide inhibition suppresses tumor growth by promoting apoptosis and pyroptosis in esophageal cancer cells

BackgroundHydrogen sulfide (H2S) has been identified as the third gaseous signaling molecule. Endogenous H2S plays a key role in the progression of various types of cancer. However, the effect of endogenous H2S on the growth of esophageal cancer (EC) remains unknown. MethodsIn this study, three kinds of H2S-producing enzymes inhibitors, DL-propargylglycine (PAG, inhibitor of cystathionine-γ-lyase), aminooxyacetic acid (AOAA, inhibitor of cystathionine-β-synthase), and L-aspartic acid (L-Asp, inhibitor of 3-mercaptopyruvate sulfurtransferase) were used to determine the role of endogenous H2S in the growth of EC9706 and K450 human EC cells. ResultsThe results indicated that the combination (PAG+AOAA+L-Asp) group showed higher inhibitory effects on the viability, proliferation, migration, and invasion of EC cells than PAG, AOAA, and L-Asp group. Inhibition of endogenous H2S promoted apoptosis via activation of mitogen-activated protein kinase pathway in EC cells. Endogenous H2S suppression triggered pyroptosis of EC cells by activating reactive oxygen species-mediated nuclear factor-κB signaling pathway. In addition, the combine group showed its more powerful growth-inhibitory effect on the growth of human EC xenograft tumors in nude mice without obvious toxicity. ConclusionOur results indicate that inhibition of endogenous H2S production can significantly inhibit human EC cell growth via promotion of apoptosis and pyroptosis. Endogenous H2S may be a promising therapeutic target in EC cells. Novel inhibitors for H2S-producing enzymes can be designed and developed for EC treatment.

Green decorated of gold nanoparticles on calcium lignosulfonate modified magnetic nanoparticles mediated by Cydonia oblonga extract: Investigation of its catalytic efficiency and its performance to treat the human esophageal cancer

This report documents an eco-friendly and sustainable protocol towards the in situ synthesized Au NPs adorned over calcium lignosulfonate (CLS) functionalized magnetite NPs, being templated by Cydonia oblonga plant extract (Fe3O4/CLS/Au NPs), followed by the evaluation of its chemical and biological properties. Physicochemical characteristics of the bio-synthesized material was assessed using an array of advanced techniques like FT-IR, SEM, TEM, EDX, elemental mapping, VSM and ICP-OES. The prepared Fe3O4/CLS/Au nanomaterial displayed an excellent catalytic performance in the formylation of amine derivatives to the related N-formyl amines. The prepared Fe3O4/CLS/Au was isolated magnetically from the reaction medium and recycled for 9 times without any significant decrease in catalytic activity. In the medicinal part, the anticancer properties of Fe3O4/CLS/Au against human esophageal cancer cell lines were determined. The IC50 of the Fe3O4/CLS/Au were 327, 228, 318, 289, 238, 208, 347, and 213μg/mL against human esophageal cancer (KYSE-30, KYSE-50, KYSE-70, KYSE-270, SK-GT-4, OE33, ESO26, and FLO-1) cell lines.

Propofol elicits apoptosis and attenuates cell growth in esophageal cancer cell lines.

Propofol is a pharmaceutical agent commonly used as an intravenous anesthetic in surgical treatments and a sedative in intensive care. However, it is largely unknown how exposure to propofol affects the proliferation, invasion, and apoptosis of neoplastic cells in esophageal cancer. In this study, we sought to elucidate the impact of propofol exposure on the growth properties of human esophageal cancer cell lines in vitro. We treated two human esophageal cancer cell lines, KYSE30 and KYSE960, with up to 10 µg/mL of propofol for 12-36 h. The treated cells were then analyzed by cell proliferation assay, Matrigel invasion assay, quantification of caspase-3/7 and -9 activities, and cell staining with Annexin V and 7-aminoactinomycin D to detect early apoptosis and cell death, respectively, via flow cytometry. We found that 3-5 µg/mL propofol reduced the growth and Matrigel invasion of both cell lines in a dose-dependent manner. Executioner caspase-3/7, but not caspase-9 involved in intrinsic apoptosis pathway, was activated by cell exposure to 3-5 µg/mL propofol. In addition, 3-5 µg/mL propofol augmented early apoptosis in both cell lines and increased cell death in the KYSE30 cell line. In summary, exposure to propofol, at concentrations up to 5 µg/mL, led to the reduction of cell growth and Matrigel invasion, as well as the augmentation of apoptosis in esophageal cancer cell lines. These data will help define a methodology to safely utilize propofol, a common general anesthetic and sedative, with esophageal cancer patients.

Nickel chloride complexes with substituted 4'-phenyl-2',2':6',2″-terpyridine ligands: synthesis, characterization, anti-proliferation activity and biomolecule interactions.

A series of Ni(II) sandwich-like coordinated compounds were synthesized by the reaction of nickel dichloride and ten 4'-(4-substituent phenyl)-2',2':6',2″-terpyridine ligands, and their structures were confirmed by elemental analysis, FT-IR, ESI-MS, solid state ultraviolet spectroscopy and X-ray single crystal diffraction analysis. Three human cancer cell lines and a normal human cell line were used for anti-proliferation potential study: human lung cancer cell line (A549), human esophageal cancer cell line (Eca-109), human liver cancer cells (Bel-7402) and normal human liver cells (HL-7702). The results show that these nickel complexes possess good inhibitory effects on the cancer cells, outperforming the commonly used clinical chemotherapy drug cisplatin. Especially, complexes 3 (-methoxyl) and 7 (-fluoro) have strong inhibitory ability against Eca-109 cell line with IC50 values of 0.223μM and 0.335μM, complexes 4 and 6 showed certain cell selectivity, and complex 6 can inhibit cancer cells and slightly poison normal cells when the concentration was controlled. The ability of these complexes binding to CT-DNA was studied by UV titration and CD spectroscopy, and CD spectroscopy was also used to study the secondary structural change of BSA under the action of the complexes. The binding of these complexes with DNA, DNA-Topo I and bovine serum protein has been simulated by molecular docking software, and the docking results and optimal binding conformation data showed that they interacted with DNA in the mode of embedded binding, which is consistent with the experimental results. These complexes are more inclined to move to the cleavage site when docking with DNA-Topo I, so as to play a role of enzyme cleavage, while BSA promotes the action of the complexes by binding to effective binding sites.

MUC13 promotes the development of esophageal cancer by upregulating the expression of o-glycan process-related molecules

BackgroundEsophageal cancer is one of the most common malignant tumors in the world, which is characterized by poor prognosis, aggressiveness, and poor survival. Mucin 13 (MUC13) is a member of the membrane-bound mucin and located on chromosome 3q21.2 and consists of α and β subunits. It has been found that MUC13 is overexpressed in a variety of tumor cells and acts a vital role in the invasiveness and malignant progression of several types of tumors. However, the role and regulatory mechanism of MUC13 in the progression of esophageal cancer remain unclear.MethodsThe expression level of MUC13 was detected in 15 esophageal cancer tissues and 15 pairs of adjacent nontumor tissues by immunohistochemistry (IHC). In addition, the expression of MUC13 mRNA level in human esophageal cancer cell lines (EC9706 and ECA109 and TE-1) was measured by qRT-PCR. In vitro, after silencing MUC13 with lentiviral interference technology, CCK8 assay, clone formation assay, and flow cytometry were applied to investigate the proliferation activity, clone formation ability and anti-apoptosis ability of EC9706 and ECA109 cells. The tumor xenograft growth assay was used to confirm the influence of MUC13 knockdown on the growth of esophageal tumors in vivo. The qRT-PCR assay and western blot experiments were taken to study the mechanism of MUC13 regulating the proproliferation and antiapoptotic of esophageal cancer.ResultsThe results showed that MUC13 was overexpressed in esophageal cancer tissues and cell lines (EC9706 and ECA109 and TE-1), especially in EC9706 and ECA109 cells, but low expressed in human esophageal epithelial cell line (HEEC). Next, silencing MUC13 inhibits proliferation, blocks cell cycle progression, and promotes cell apoptosis in vitro, and restrains the growth of esophageal cancer tissues in vivo. Finally, MUC13 affects the proproliferation and antiapoptotic by regulating the expression of GLANT14, MUC3A, MUC1, MUC12, and MUC4 that closely related to O-glycan process.ConclusionsThis study proved that MUC13 is an important molecule that regulates the O-glycan process and then affects the progress of esophageal cancer. MUC13 may be a novel therapeutic target for patients with esophageal cancer.

Ribonucleotide reductase subunit M1 blocks glucose catabolism via phosphorylation of pyruvate kinase M2 in human esophageal squamous cell cancer

Ribonucleotide reductase subunit M1 blocks glucose catabolism via phosphorylation of pyruvate kinase M2 in human esophageal squamous cell cancer

Phospholysine phosphohistidine inorganic pyrophosphate phosphatase suppresses human esophageal cancer cell growth by inducing mitotic catastrophe through the P27/cyclin A/CDK2 signaling pathway

Esophageal cancer (ESCA) is a global dead malignancy with poor prognosis. However, its underlying molecular mechanism remains to be elucidated. Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) has been reported as a tumor suppressor in multisystem cancer but its function in ESCA has not been reported. We analyzed LHPP expression between normal and tumor tissues of ESCA patients and performed LHPP overexpression on the ESCA cells KYSE-150 (K150). We did not observe significant differences in the expression level of LHPP between ESCA and normal tissue, and noticed that LHPP expression was not related to ESCA patient survival rate. However, increased expression of LHPP in K150 cells induced mitochondrial dysfunction, inhibited cell proliferation, migration, and cell cycle, and simultaneously increased cell apoptosis. Besides, we found that K150 cells underwent mitotic catastrophe after overexpressing LHPP, which may be regulated through the P27/cyclin A/cdk2 signaling pathway. Although the expression of LHPP may not be related to the progression and prognosis of ESCA, mitotic catastrophe, a new mechanism of tumor suppressor function of LHPP was found after overexpressing LHPP in ESCA cells. Data AvailabilityThe data used to support the findings of this study are included within the article.

Nano-particulate Toll-like Receptor 9 Agonist Potentiates the Antitumor Activity of Anti-Glypican-1 Antibody.

Monoclonal antibodies (mAbs) that target tumor antigens have recently been developed. Their antitumor activity is mainly achieved through antibody-dependent cellular cytotoxicity (ADCC) via effector cells such as tumor-infiltrated macrophages and natural killer (NK) cells. CpG oligodeoxynucleotides (ODNs) have potent antitumor activity and are considered to increase the tumor infiltration of macrophages and NK cells; however, a completely solubilized novel CpG-schizophyllan (SPG) complex, K3-SPG, displays more potent antitumor activity. We recently reported the significant antitumor activity of anti-glypican-1 (GPC1) mAb against GPC1-positive esophageal squamous cell carcinoma (ESCC) via ADCC. The aim of this study was to evaluate the potential synergistic antitumor activity of anti-GPC1 mAb and K3-SPG and elucidate the underlying mechanisms using a xenograft model of GPC1-positive human ESCC cells. The established human esophageal cancer cell line TE14 was subcutaneously injected into SCID mice. Xenograft mice were treated with anti-GPC1 mAb, K3-SPG, or their combination. Antitumor activity was evaluated by measuring the tumor volume. For FACS analysis, agents were administrated, and tumors were resected 1 day after the final treatment. Anti-GPC1 mAb or K3-SPG monotherapy showed dose-dependent antitumor activity, and combination therapy with anti-GPC1 mAb and K3-SPG showed antitumor activity (p=0.0859). Flow cytometry revealed significantly increased numbers of macrophages (p=0.0133) and of the ratio of activated NK cells/total NK cells (p=0.0058) following K3-SPG or combination therapy. Combination therapy with K3-SPG and anti-GPC1 mAb or another antitumor mAb may represent a new cancer treatment option acting via ADCC.

Bioinformatics analysis of necroptosis‑related lncRNAs and immune infiltration, and prediction of the prognosis of patients with esophageal carcinoma.

Esophageal carcinoma (ESCA) is one of the most common malignancies in the world, and has high morbidity and mortality rates. Necrosis and long noncoding RNAs (lncRNAs) are involved in the progression of ESCA; however, the specific mechanism has not been clarified. The aim of the present study was to investigate the role of necrosis-related lncRNAs (nrlncRNAs) in patients with ESCA by bioinformatics analysis, and to establish a nrlncRNA model to predict ESCA immune infiltration and prognosis. To form synthetic matrices, ESCA transcriptome data and related information were obtained from The Cancer Genome Atlas. A nrlncRNA model was established by coexpression, univariate Cox (Uni-Cox), and least absolute shrinkage and selection operator analyses. The predictive ability of this model was evaluated by Kaplan-Meier, receiver operating characteristic (ROC) curve, Uni-Cox, multivariate Cox regression, nomogram and calibration curve analyses. A model containing eight nrlncRNAs was generated. The areas under the ROC curves for 1-, 3- and 5-year overall survival were 0.746, 0.671 and 0.812, respectively. A high-risk score according to this model could be used as an indicator for systemic therapy use, since the half-maximum inhibitory concentration values varied significantly between the high-risk and low-risk groups. Based on the expression of eight prognosis-related nrlncRNAs, the patients with ESCA were regrouped using the 'ConsensusClusterPlus' package to explore potential molecular subgroups responding to immunotherapy. The patients with ESCA were divided into three clusters based on the eight nrlncRNAs that constituted the risk model: The most low-risk group patients were classified into cluster 1, and the high-risk group patients were mainly concentrated in clusters 2 and 3. Survival analysis showed that Cluster 1 had a better survival than the other groups (P=0.016). This classification system could contribute to precision treatment. Furthermore, two nrlncRNAs (LINC02811 and LINC00299) were assessed in the esophageal epithelial cell line HET-1A, and in the human esophageal cancer cell lines KYSE150 and TE1. There were significant differences in the expression levels of these lncRNAs between tumor and normal cells. In conclusion, the present study suggested that nrlncRNA models may predict the prognosis of patients with ESCA, and provide guidance for immunotherapy and chemotherapy decision making. Furthermore, the present study provided strategies to promote the development of individualized and precise treatment for patients with ESCA.

Amino Acid Derivatives of Chlorin-e6-A Review.

Details of the structural elucidation of the clinically useful photodynamic therapy sensitizer NPe6 (15) are presented. NPe6, also designated as Laserphyrin, Talaporfin, and LS-11, is a second-generation photosensitizer derived from chlorophyll-a, currently used in Japan for the treatment of human lung, esophageal, and brain cancers. After the initial misidentification of the structure of this chlorin-e6 aspartic acid conjugate as (13), NMR and other synthetic procedures described herein arrived at the correct structure (15), confirmed using single crystal X-ray crystallography. Interesting new features of chlorin-e6 chemistry (including the intramolecular formation of an anhydride (24)) are reported, allowing chemists to regioselectively conjugate amino acids to each available carboxylic acid on positions 131 (formic), 152 (acetic), and 173 (propionic) of chlorin e6 (14). Cellular investigations of several amino acid conjugates of chlorin-e6 revealed that the 131-aspartylchlorin-e6 derivative is more phototoxic than its 152- and 173-regioisomers, in part due to its nearly linear molecular conformation.

Au/ZnO Nanocomposites Prepared by Laser Ablation for Enhancement of Antibacterial Activity and Cytotoxic Properties against Cancer Cells

This study presents a comprehensive look into the potential therapeutic, antibacterial, and anticancer properties of a nanocomposite (NC) of gold (Au) and zinc oxide (ZnO). In this study, we analyzed the adherence between Au nanoparticles (NPs) and ZnO NPs. X-ray diffraction analysis showed high crystallinity and small crystallite sizes of Au NPs and ZnO NPs, while transmission electron microscopy showed spherical NPs. Furthermore, histogram analysis showed that the average particle size of Au NPs is 27 nm, while that of ZnO NPs is 35 nm. The adherence of ZnO NPs on the surface of Au NPs increased their combined particle size to 51 nm and revealed a high-population core-shell structure. The activity of Au/ZnO NCs against Escherichia coli was more potent when compared to that of elemental Au and ZnO NPs alone. The cytotoxic effects of Au NPs, ZnO NPs, and Au/ZnO NCs against human breast cancer cells (AMG13) and human esophageal adenocarcinoma cancer cells (SK-GT4) were investigated in this study. We found that AMG13 is more sensitive than SK-GT4 to the activity of Au/ZnO NCs. The cytotoxicity of Au/ZnO NCs against AMG13 was 89%, while that against SK-GT4 was 85%. Less cytotoxic effects were recorded against normal cells (MCF7) when compared with those of cancer cells. Based on these findings, the synthesized Au/ZnO NCs could be used as a promising strategy for biomedical applications.

Abstract PL03-01: New insights into carcinogenesis from normal esophagus

Abstract All normal tissues studied to date carry somatic mutant clones, the burden of which increases with age. This talk considers how insights into the biology of mutants in normal tissues can inform our understanding of the earliest stages of carcinogenesis. The esophagus becomes a patchwork of mutant clones. As they expand, these clones compete for the limited space available, resulting in selection of the fittest mutant genes. The ability to out compete other mutants in normal tissue does not correlate with carcinogenic potential. For example, NOTCH1 mutant clones colonize most of the esophagus by middle age but NOTCH1 mutations are comparatively rare in squamous cancers. In mouse models Notch pathway mutant clones eliminate microscopic intraepithelial neoplasms and loss of Notch1 markedly slows esophageal tumor growth. In contrast, mutant TP53 is less effective than NOTCH1 at driving clonal expansion but is found in almost all human squamous esophageal cancers and contributes to carcinogenesis in mice. The normal tissue mutational landscape of the esophagus is shaped by environmental factors. For example, body metabolism alters the behavior of mutant PIK3CA which drives clonal expansions in the esophagus of overweight humans and mice. The mutation causes cells to switch their metabolism to aerobic glycolysis, giving the mutants a proliferative advantage. One way to reduce the competitive advantage of mutants is to increase the fitness of the neighboring cells. Treating cells or mice with metformin, a drug used to treat type 2 diabetes, induces aerobic glycolysis throughout the tissue. This eliminates the growth advantage of Pik3ca mutant clones, showing it may be possible to halt the expansion of oncogenic mutant populations. Beyond the esophagus, these findings suggest the need to consider the relative prevalence of mutations in normal tissue and the corresponding cancer(s) before deciding if a mutant gene is a cancer driver or not. Variation in cancer risk between different human populations may depend on the proportion of pro- and anti-oncogenic mutants in normal tissue. Understanding how certain mutations can impede cancer development and how environmental factors alter selection of oncogenic mutants in normal tissue may guide new approaches to cancer prevention. Citation Format: Phil H. Jones. New insights into carcinogenesis from normal esophagus. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr PL03-01.

Enhancing the Efficiency of Doxorubicin -Conjugated with gold nanocomposites for Active Targeting and Laser Treatment for Human Esophagus Cancer Cells

Nanotechnology is being used in cancer treatment to deliver drugs to tumors, improve imaging, and detect cancer cells. Nanoparticles are being used to deliver drugs more effectively to tumors, while also reducing the side effects of the drugs. The current context shows the conceivable biomedical utility of gold nanoparticles (AuNPs) covered with doxorubicin (DOX) for double chemotherapy and photothermal therapy (PTT) of throat cancers (esophagus) in vitro. DOX as FDA-authorized anti-cancer drug was added to AuNPs to enhance the chemotherapy impact. The blended DOX - AuNPs showed exorbitant cytotoxicity at the cancer cells and strong light absorption for temperature expansion in vitro. In the wake of treating DOX– Au nanocomposites with inside the esophagus cell line, PTT-helped DOX-Au nanocomposites involved the fantastical cytotoxicity of the cell strains for 15 min after the laser treatment. Exceptionally cytotoxicity impact in esophagus cell line turned out to be more attractive due to specific light absorption with the aid of using the directed DOX-Au nanocomposites. Thusly, the proposed DOX-Au nanocomposites might be an ability nano-theranostic material for treating throat cancers. The gene expression levels withinside the esophagus cell line from every group with or without laser exposure have been compared individually with control group. Bax has been overexpressed in esophagus cell line organization post 15 min laser irradiation. Conversely, BCL-2 gene has been down regulated with the aid of using RT-PCR analysis post 15 min laser irradiation, while in comparison to control cell line.

Oncolytic adenovirus-mediated dual knockdown of survivin and OCT4 improves therapeutic efficacy in esophageal cancer.

Survivin and octamer-binding transcription factor 4 (OCT4) are reportedly up-regulated in esophageal cancer (EC) and have been correlated with high tumor proliferative activity and poor prognosis. Oncolytic viruses encoding specific transgenes have been considered as therapeutic methods to increase therapeutic efficacy in a variety of solid tumors. In this study, an oncolytic adenovirus carrying short hairpin RNA (shRNA) of survivin (shSRVN) and OCT4 (shOCT4) was constructed to achieve dual knockdown of survivin and OCT4 and to explore the potential effect of the oncolytic adenovirus in EC. The oncolytic adenovirus replicated abundantly in human EC cells, with the replication multiplying by up to 192,085 and 620,055 times in esophageal carcinoma (Eca)-109 cells transfected with purified and completed recombinant adenoviruses called AdSProE1a-dual shRNA (shSRVN + shOCT4) and TE1 cells transfected with AdSProE1a-survivin shRNA (shSRVN) 96 hours after infection, respectively. The shRNAs targeting survivin and OCT4 significantly downregulated the expression levels of survivin and OCT4 in cells, thereby inhibiting the proliferative activity of cancer cells. Furthermore, E-cadherin and vimentin, which are both considered epithelial mesenchymal transition (EMT) markers, were found to be upregulated and downregulated, respectively, in cancer cells after exposure to the viral infection. The interference of survivin and OCT4 also contributed to cell cycle arrest and apoptosis, the half maximal inhibitory concentrations (IC50s) of oncolytic adenovirus loaded with AdSProE1a-shSRVN + shOCT4 in the Eca109 cells and the TE1 cells were 0.7271 and 0.1032 pfu/mL, respectively. Xenograft experiments in vivo showed that oncolytic adenovirus-mediated dual knockdown of survivin and OCT4 effectively inhibited the growth of xenografts and induced cancer cell apoptosis. We concluded that therapies targeting survivin and OCT4 have great potential for improving the therapeutic efficacy in EC. The dual target design strategy ensured the efficacy and safety of the treatment system and provided a novel and effective adjuvant target therapy for EC.

An alternative technique for cyclization synthesis, in vitro anti-esophageal cancer evaluation, and molecular docking of novel thiazolidin-4-one derivatives

In this work, two novel series of thiazolidin-4-one derivatives (9a–e and 10a–e) constituting ten compounds were synthesized under batch and ultrasound irradiation. It is found that the use of sonochemical methodology in the thiazolidin-4-ones synthesis offers several ecological advantages such as an effective, inexpensive, easy applicable, eco-friendly, and waste-free chemicals than the batch method. Different techniques including NMR (1H and 13C), mass spectra, and infrared radiation (FTIR) were employed to characterize the chemical structures of all the synthesized thiazolidin-4-one derivatives. The purified derivatives were tested for their anti-esophageal cancer activity against a panel of human esophageal cancer cell line (SKGT-4). The in vitro cytotoxic and apoptotic activities of these derivatives were evaluated by MTT and AO/EB assays, respectively. Among these derivatives, thiazolidin-4-one derivatives 9e and 10b were found to have the most potency toward SKGT-4 human esophageal cells. When compared to the reference standard (cisplatin, IC50 5.21±0.41 µg/mL), the values (IC50) of the derivatives 9e and 10b were found as 17.6 ± 0.06 and 18.5 ± 0.01 μg/mL, respectively. The collected data from AO/EB assay revealed these derivatives are able to stimulate the apoptotic effect in the SKGT-4 cells with a selective pathway compared to their behaviors in the normal Vero cells. Moreover, DFT-assisted calculations with theoretical level: B3LYP/6–31G(d,p) were adopted to optimize the geometrical structures of the derivatives 9e and 10b. To elucidate the possible binding mechanisms of these derivatives 9e and 10b with the active sites of human esophageal proteins (PDB ID: 6DUK, 2LEO, and 5HZN), the docking study was accomplished. According to the docking analysis, the derivatives 9e and 10b showed efficient interactions with the target receptors with low values of binding affinity. Thus, the biological tests and docking scores suggested that the synthesized thiazolidin-4-one derivatives 9e and 10b may be considered as a potential candidate for esophageal cancers treatments.

Baicalein Inhibits the Growth of Transplanted Esophageal Cancer in Mice and the Effect on the Expression of PAK4

We studied the mechanism underlying the effect of baicalein on the growth of transplanted esophageal cancer in NOG mice and its effect on the expression of PAK4. For that purpose, we developed a new model of transplanted esophageal cancer (human esophageal cancer OE19 cells (107 cells/ml) were inoculated to NOG mice). Three experimental groups with transplanted esophageal cancer cells received baicalein in different doses (1, 1.5, and 2 mg/kg). In 32 days, the tumors were resected, and the expression of PAK4 and the level of activated PAK4 were assayed by reverse transcription PCR and Western blotting, respectively. The results showed a dose-depending anti-tumor effect of baicalein on the transplanted esophageal cancer in NOG mice: this effect of baicalein (determined by the size and weight of the tumor) increased with increasing the dose of the substance. Furthermore, the anti-tumor effect of baicalein was also confirmed by reduction of PAK4 expression. Thus, baicalein can inhibit tumor growth by inhibiting activation of PAK4. Therefore, our results showed that baicalein could inhibit the growth of esophageal cancer cells by inhibiting the activity of PAK4, which can be an important mechanism of its antitumor effect.

A New Model of Esophageal Cancers by Using a Detergent-Free Decellularized Matrix in a Perfusion Bioreactor.

The lack of physiologically relevant human esophageal cancer models has as a result that many esophageal cancer studies are encountering major bottleneck challenges in achieving breakthrough progress. To address the issue, here we engineered a 3D esophageal tumor tissue model using a biomimetic decellularized esophageal matrix in a customized bioreactor. To obtain a biomimetic esophageal matrix, we developed a detergent-free, rapid decellularization method to decellularize porcine esophagus. We characterized the decellularized esophageal matrix (DEM) and utilized the DEM for the growth of esophageal cancer cell KYSE30 in well plates and the bioreactor. We then analyzed the expression of cancer-related markers of KYSE30 cells and compared them with formalin-fixed, paraffin-embedded (FFPE) esophageal squamous cell carcinoma (ESCC) tissue biospecimens. Our results show that the detergent-free decellularization method preserved the esophageal matrix components and effectively removed cell nucleus. KYSE30 cancer cells proliferated well on and inside the DEM. KYSE30 cells cultured on the DEM in the dynamic bioreactor show different cancer marker expressions than those in the static well plate, and also share some similarities to the FFPE-ESCC biospecimens. These findings built a foundation with potential for further study of esophageal cancer behavior in a biomimetic microenvironment using this new esophageal cancer model.